The goal of this proposal is to investigate the role of viral infection in the pathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Cells to be evaluated include synovial cells, chondrocytes, and lymphoreticular cells from peripheral blood and synovial tissues. Using multiple techniques, we will search for nonspecific abnormalities in RA and SLE cells and also for specific viruses. Immunologic techniques will be used to search for an immunospecific response of RA lymphocytes to autologous RA synovial cells. Antibody-dependent cellular cytotoxicity and direct cell-mediated cytotoxicity (CMC) assays by 51Cr-release will be used. In vitro secondary stimulation of RA lymphocytes on autologous synovial cells will be used to increase the CMC assay sensitivity. If a cell strain is identified which appears to contain RA specific immunogens, the possibility that these cells contain viral antigens can be explored by the viral probe procedures that we will be pursuing simultaneously. Another technique is the use of radiolabelled viral nucleic acid probes in nucleic acid hybridization studies with DNA extracted from SLE or RA tissues. Our first study will explore the possibility of measles virus infection of SLE lymphocytes. Other potential studies include evaluating the hypothesis of measles virus infection of RA synovial tissue, and oncornavirus infection of SLE lymphocytes.